Apolipoprotein E Genotype and Cognitive Performance in Breast Cancer Survivors

乳腺癌幸存者的载脂蛋白 E 基因型和认知表现

• 批准号: 7114667
• 负责人: BRENT John SMALL
• 金额: $ 7.25万
• 依托单位: UNIVERSITY OF SOUTH FLORIDA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7114667
• 关键词: apolipoprotein E; breast neoplasms; clinical research; genotype; neoplasm /cancer; performance

DESCRIPTION (provided by applicant): In recent years there has been considerable interest in the e4 allele of Apolipoprotein E (APOE), a genetic risk factor for Alzheimer's disease, as a risk factor for cognitive impairment in healthy aging. Recently, there has been growing recognition that women diagnosed with early stage breast cancer may experience cognitive problems as a consequence of adjuvant chemotherapy. In addition, research suggests that the presence of the e4 allele of APOE may also convey a disadvantage to the cognitive performance of breast cancer survivors. In the current proposal we examine cross-sectional differences and longitudinal changes in the cognitive functioning of a sample of breast cancer survivors and healthy controls as a function of APOE- e4 genotype. Specifically, we will assess APOE genotype of a group of breast cancer survivors who have been examined for over 3 years since the inception of treatment, as well as a matched sample of healthy controls who have been examined at a single measurement point. The specific aims are: 1) To compare cross-sectional differences in the cognitive performance of breast cancer survivors and healthy controls as a function of APOE-e4 genotype; 2) To examine longitudinal changes in cognitive performance among breast cancer survivors as a function of APOE-e4 genotype; and 3) To examine the role of cancer treatment-related and cardiovascular disease factors in the presence and severity of APOE-e4-related changes in cognitive performance among breast cancer survivors. Cognitive performance is indexed with multiple tests of episodic memory, attention, complex cognition, motor speed, and language. We predict that relative to healthy controls, the cognitive performance of breast cancer survivors will be poorer and breast cancer survivors who are APOE-e4 positive will perform most poorly. In terms of longitudinal changes, we predict that breast cancer survivors who are APOE-e4 positive will exhibit greater declines longitudinally, relative to non-e4 carriers. The results of the current proposal are relevant to attempts to describe factors that may predispose cancer survivors to negative cognitive outcomes after treatment. Identifying factors that may increase a person's risk of cognitive impairment following treatment for cancer is a great concern to public health. In the current proposal, we examine the potential of APOE-e4 genotype, known risk factor for Alzheimer's disease, to predispose breast cancer survivors for poor cognitive outcomes.

描述（由申请人提供）：近年来，E4载脂蛋白E（APOE）的E4等位基因是阿尔茨海默氏病的遗传危险因素，这是健康衰老认知障碍的危险因素。最近，人们越来越认识到被诊断出患有早期乳腺癌的妇女可能由于辅助化疗而遭受认知问题。此外，研究表明，APOE的E4等位基因的存在也可能使乳腺癌幸存者的认知表现不利。在当前的建议中，我们检查了乳腺癌幸存者样本和健康对照样本的认知功能的横断面差异和纵向变化，这是APOE-E4基因型的函数。具体而言，我们将评估一组乳腺癌幸存者的APOE基因型，这些乳腺癌幸存者自治疗成立以来已经进行了3年的检查，以及在单个测量点进行了检查的匹配的健康对照样本。具体目的是：1）比较乳腺癌幸存者的认知性能和健康对照的横截面差异，这是APOE-E4基因型的函数； 2）检查乳腺癌幸存者在APOE-E4基因型的函数中认知表现的纵向变化； 3）检查乳腺癌幸存者认知性能变化的存在和严重程度，与癌症治疗相关和心血管疾病因素的作用。认知表现通过多个情节记忆，注意力，复杂的认知，运动速度和语言进行了多次索引。我们预测，相对于健康对照组，乳腺癌幸存者的认知表现较差，而APOE-E4阳性的乳腺癌幸存者的表现最差。就纵向变化而言，我们预测，相对于非E4载体，APOE-E4阳性的乳腺癌幸存者纵向下降。当前建议的结果与试图描述可能使癌症幸存者在治疗后产生负面认知结果的因素有关。确定可能增加一个人治疗癌症认知障碍风险的因素是公共卫生的极大关注。在当前的提案中，我们研究了APOE-E4基因型（已知的阿尔茨海默氏病风险因素）的潜力，使人们倾向于乳腺癌幸存者的认知结果不良。